Trp-Lys-Tyr-Met-Val-d-Met is a chemoattractant for human phagocytic cells

Abstract

Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a synthetic peptide that stimulates phosphoinositide (PI) hydrolysis in human leukocytes. The peptide binds to a unique cell surface receptor(s). Recently we had demonstrated that human neutrophils, monocytes, and B lymphocytes express this peptide-specific receptor and that stimulation of human leukocytes with the peptide leads to activation of the oxidative respiratory system and the bactericidal activity of neutrophils or monocytes. In this study we showed that the peptide induces chemotaxis of phagocytic leukocytes and studied the signaling pathway leading to chemotaxis in human monocytes. The peptide-induced monocyte chemotaxis is pertussis toxin (PTX)-sensitive. This fact correlates with the peptide's stimulation of PI hydrolysis and intracellular Ca2+ ([Ca2+]i) release, which is also PTX-sensitive. We demonstrate that the peptide-specific receptor is different from receptor(s) for monocyte chemoattractant protein-1 (MCP-1). We also show that intracellular signaling of WKYMVm leading to monocyte chemotaxis is different from that of MCP-1. The peptide-mediated monocyte chemotaxis is insensitive to protein kinase C (PKC) inhibitor (GF109203X) and butan-1-ol, ruling out PKC and phospholipase D participation in this process. On the other hand, a tyrosine kinase inhibitor (genistein) and RhoA inhibitor (C3 transferase) curtailed the peptide-induced chemotaxis in a concentration-dependent manner, implying the involvement of tyrosine kinase and RhoA, respectively. Treatment of human monocytes with the peptide stimulates tyrosine phosphorylation of several cellular proteins, including p125FAK and Pyk2 and translocation of RhoA from the cytosol to the membrane. We conclude that WKYMVm induces chemotaxis of human phagocytic leukocytes via unique receptors and signaling.

The Synthetic Peptide Trp-Lys-Tyr-Met-Val-D-Met Inhibits Human Monocyte-Derived Dendritic Cell Maturation via Formyl Peptide Receptor and Formyl Peptide Receptor-Like 2

“…Some viral chemokine homologues bind to chemokine or chemoattractant receptors, alter receptor activation properties, and inhibit the proper functioning of receptor-mediated immune responses (47). Because HIV T-20 peptide and H. pylori Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) peptide are ligands of FPR and FPRL2, respectively, it appears that these pathogen-derived agonists suppress DC-mediated immune responses by activating FPR or FPRL2.…”

“…Previous studies have demonstrated that WKYMVm induces human monocytes and neutrophils to generate cellular superoxide and to undergo chemotactic migration (11)(12)(13). Three cell surface G-protein-coupled WKYMVm receptors have been identified (14 -16), namely, formyl peptide receptor (FPR), FPR-like 1 (FPRL1), and FPR-like 2 (FPRL2) (14 -16).…”

Protein Kinase C β Is Required for Human Monocyte Chemotaxis to MCP-1

“…A synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met, has been shown to be a chemotactic stimulus to phagocytic leukocytes including human monocytes (54). Even though the peptideinduced monocyte chemotaxis is pertussis toxin-sensitive, the peptide-specific receptor is different from receptors for MCP-1 and is insensitive to GF109203X.…”

Differential Activation of Formyl Peptide Receptor Signaling by Peptide Ligands

“…WKYMVm has been reported to induce the chemotactic migration of phagocytic cells, such as monocytes and neutrophils (Bae et al, 1999b). Le et al (2000) demonstrated that WKYMVm induced cellular chemotaxis by binding to FPR.…”